Utz Settmacher

Venous complications after orthotopic liver transplantation

Complications involving the portal vein or the vena cava, are rare after orthotopic liver transplantation. We report on the incidence and treatment of venous complications following 1000 orthotopic liver transplantations in 911 patients. Twenty‐six of the adult patients (2.7%) suffered from portal complications after transplantation, whereas complications of the vena cava were observed in only 17 patients (1.8%). Technical problems or recurrence of the underlying disease (e.g. Budd–Chiari syndrome) accounted for the majority of complications of the vena cava, whereas alteration of the vessel wall or splenectomy during transplantation could be identified as important risk factors for portal vein complications. In patients undergoing modification of the standard end‐to‐end veno‐venous anastomosis of the portal vein due to pathological changes of the vessel wall, complications occurred in 8.3%, whereas only 2.4% of patients who received a standard anastomosis of the portal vein experienced complications of the portal vein. Furthermore, splenectomy during transplantation was also associated with an increased incidence of portal vein complications (10.5 vs. 2.2% in patients without splenectomy). Treatment was dependent on the signs and symptoms of the patients, and varied considerably between patients with portal vein complications and patients suffering from complications of the vena cava. Complications of the vena cava led to retransplantation in about one‐third of the patients, whereas in patients with occlusion of the portal vein, retransplantation was necessary in only 15%, and more than half of the patients suffering from portal vein complications did not require any treatment at all. Usually, treatment of patients with portal vein complications only became necessary when additional complications such as arterial occlusion or bile duct injuries occurred.

Clinical Implications of Hepatic Preservation Injury After Adult Liver Transplantation

Several advances in organ preservation have allowed for improved results after liver transplantation; however, little information is available regarding the clinical impact of preservation injury on the postoperative course. The medical records of 889 liver transplants were retrospectively reviewed. Preservation injury was classified according to postoperative aspartate aminotransferase values as minor (<1000 U/L), moderate (1000–5000 U/L), or severe (>5000 U/L). The following criteria were analyzed and compared according to the extent of preservation injury: patient and graft survival, retransplantation rate, duration of hospitalization and postoperative ventilation, as well as incidence of rejection, infection, and hemodialysis. The majority of patients received a liver with minor preservation injury (75.9%), whereas 22.7% and 1.3% of grafts showed moderate or severe injury. Graft survival was significantly lower in patients with severe preservation injury, when compared to minor or moderate injury. The relative risk for initial nonfunction was 39.36‐fold increased (95% confidence interval (ci): 10.3–150.2), as it was increased for duration of postoperative ventilation (6.92‐fold; 95%ci: 2.1–22.3) and hemodialysis (6.13‐fold; 95%ci: 1.9–19.3). Since the incidence of retransplantation was significantly increased (50%), patient survival remained comparable between all groups. Severe preservation injury had a tremendous impact on the postoperative clinical course, requiring the maximum medical effort to achieve adequate patient survival.

Expression of CD40 in Vascular Smooth Muscle Cells and Macrophages Is Associated With Early Development of Human Atherosclerotic Lesions

CD40-CD154-mediated signaling has recently been described as playing a role in cellular functions involved in atherosclerotic processes. CD40 is expressed in macrophages, lymphocytes, endothelial cells, and vascular smooth muscle cells. However, cross-sectional studies investigating the expression of CD40 in atherosclerotic lesions are lacking. In the present study the expression of CD40 was studied in atherosclerotic lesions from 43 patients classified according to the World Health Organization criteria. Serial immunohistologic stainings of human iliac arteries from 43 patients were performed using monoclonal antibodies. Lesions were classified according to World Health Organization criteria, and CD40 expression was analyzed with regard to cell morphology and cellular markers by 2 independent observers. Human atherosclerotic lesions revealed a significant increase in intimal thickness, number of inflammatory infiltrates, and CD40-positive macrophages and vascular smooth muscle cells with progression of the lesions. This increase was most prominent from stage 0 to stage I. A significant correlation between intimal thickness and CD40-positive macrophages (r = 0.75, p <0.0005) and CD40-positive vascular smooth muscle cells (r = 0.81, p <0.0005) was observed. Ligation of the cellular CD40 receptor contributes to inflammatory cellular events in human vascular smooth muscle cells. These data suggest a direct association of CD40 expression in atherosclerotic lesions with early plaque development.

Initial hepatic microcirculation correlates with early graft function in human orthotopic liver transplantation

Microcirculatory disturbances are an initial causative determinant in hepatic ischemia/reperfusion injury. The aim of this study was to assess sinusoidal perfusion during human liver transplantation using orthogonal polarization spectral imaging and to evaluate the significance of intraoperative microcirculation for early postoperative graft function. Hepatic microcirculation was measured in 27 recipients undergoing full‐size liver transplantation and compared to a group of 32 healthy living‐related liver donors. The microvascular parameters were correlated with postoperative aspartate aminotransferase and bilirubin levels. Hepatic perfusion following liver transplantation was found to be significantly decreased when compared with the control group. Volumetric blood flow within the individual sinusoids increased due to sinusoidal dilatation and enhanced flow velocity. Regression analysis of postoperative aspartate aminotransferase and bilirubin with microvascular parameters revealed significant correlations. The extent of volumetric blood flow increased within the first 30 minutes after reperfusion and showed a significant correlation with postoperative aspartate aminotransferase release and bilirubin elimination. In conclusion, postischemic hepatic microvascular perfusion was analyzed in vivo, demonstrating significant microvascular impairment during liver transplantation. Sinusoidal hyperperfusion appears to confer protection against postischemic liver injury, as given by the correlation with aspartate aminotransferase and bilirubin levels. Thus, these findings may have therapeutic importance with respect to mechanisms mediating postischemic reactive hyperemia. (Liver Transpl 2005;11:555–563.)

Technique of bile duct reconstruction and management of biliary complications in right lobe living donor liver transplantation

Abstract:  From December 1999 to January 2002, 50 right lobe living donor liver transplantations were performed. The donor operations included an intraoperative cholangiography to elicit variations in bile duct anatomy. The biliary reconstruction was done whenever possible as an end‐to‐end microanastomosis of the donor right hepatic duct with the recipients bile duct. As a result of the early segmental branching of the donor biliary tree, two segment bile ducts had to be anastomosed in 20 patients and three segment bile ducts in three patients. In 12 patients, a Roux‐en‐Y hepaticojejunostomy was performed. All anastomoses were drained externally. We observed two leakages at the resection surface which could be treated successfully by an external drainage. Six leaks occurred at the site of end‐to‐end biliary anastomoses. Twice the problem could be conservatively solved placing a stent percutaneously. In two patients a hepaticojejunostomy was performed after a bile duct necrosis. In two patients with an anastomotic leak, occurring 3 d, respectively, 3 month after the original transplantation, the bile duct could be directly reconstructed over a T‐tube. Two anastomotic stenoses were observed, one in combination with a leak treated by percutaneous stent implantation and the second, 3 month after transplantation which was treated surgically. Biliary reconstruction after living donor liver transplantation requires microsurgical techniques and can be performed as a direct end‐to‐end anastomosis in most cases. Biliary complications were treated by percutaneous drainage or surgical revision in all cases.

In Vivo Imaging of Human Pancreatic Microcirculation and Pancreatic Tissue Injury in Clinical Pancreas Transplantation

Pancreatitis remains to be a major complication following clinical pancreas transplantation. We performed orthogonal polarized spectral (OPS) imaging for direct in vivo visualization and quantification of human pancreatic microcirculation in six healthy donors for living donor liver transplantation and 13 patients undergoing simultaneous pancreas‐kidney transplantation. We further determined the impact of microvascular dysfunction during early reperfusion on pancreatic graft injury. Exocrine and endocrine pancreatic impairment was determined by analysis of serum lipase, amylase and C‐peptide levels. Compared to normal pancreas in liver donors (homogeneous acinar perfusion) functional capillary density (FCD) and capillary red blood flow velocity of reperfused grafts were significantly decreased. Elevated CRP concentrations on day 2 post‐transplant and serum lipase and amylase levels determined on days 4–5 significantly correlated with microvascular dysfunction during the first 30 min of graft reperfusion. Post‐transplant serum C‐peptide also correlated significantly with pancreatic capillary perfusion. OPS imaging allows to intra‐operatively assess physiologic pancreatic microcirculation and to determine microcirculatory impairment during early graft reperfusion. This impairment correlated with the manifestation of post‐transplant dysfunction of both exocrine and endocrine pancreatic tissue. OPS imaging may be used clinically to determine the efficacy of interventions, aiming at attenuating microcirculatory impairment during the acute post‐transplant reperfusion phase.

Mycophenolate mofetil in combination with tacrolimus versus neoral after liver transplantation

MYCOPHENOLATE mofetil (MMF) is an accepted immunosuppressive agent after kidney transplantation. Possible indications for MMF after liver transplantation include: (1) rejection therapy; (2) reduction of cyclosporine or tacrolimus dosage in patients with nephro-, neuro-, or hepatotoxicity; and (3) early steroid withdrawal. The potential role of additive MMF therapy in patients with HCV cirrhosis has been explored; however, data concerning MMF induction or maintenance therapy are limited.

Percutaneous Transluminal Laser Angioplasty versus Balloon Dilation for Treatment of Popliteal Artery Occlusions

Purpose: To compare the immediate results, complication rates, and long-term outcomes of percutaneous transluminal laser angioplasty (PTLA) versus balloon dilation alone in the treatment of popliteal artery occlusions. Methods: In a prospective nonrandomized study conducted between December 1994 and June 2000, 215 symptomatic patients with unilateral popliteal occlusions were treated with either dilation alone (88 patients: 52 men; mean age 62 years, range 48–83) or PTLA (127 patients: 70 men; mean age 64 years, range 49–86) using a 308-nm excimer laser followed by dilation. The average occlusion length was 10.4 cm (range 3–14). Results: PTLA was successful in recanalizing 105 (82.7%) arteries, while the recanalization rate for dilation alone was only 70.4% (62/88; p=0.045). After a mean follow-up of 36 months (range 6–52), the primary and secondary patency rates were 21.7% and 50.8%, respectively, in patients with PTLA and 16.3% and 35.2% in the angioplasty group (p=0.762). The complication rates associated with both techniques were similar. Conclusions: Although initial recanalization may be better with PTLA, it does not appear to add any long-term benefit over balloon dilation alone.

Prospective Evaluation of the Clinical Utility of Different Methods for the Detection of Human Cytomegalovirus Disease after Liver Transplantation

Standardized human cytomegalovirus (HCMV) assays were prospectively evaluated to predict HCMV disease. In 135 consecutive adult liver transplantations, pp65‐antigenemia, quantitative HCMV‐DNA and qualitative pp67‐messenger‐RNA were determined weekly. No ganciclovir prophylaxis or preemptive treatment was used. One hundred and ten (81.5%) patients showed no HCMV‐infection, 25 patients were positive in at least one of the HCMV‐tests (18.5%). Four suffered from HCMV viral syndrome (3.0%) and another four from tissue invasive disease. In total, pp65‐antigenemia was detected in 18, HCMV‐DNA in 22 and pp67‐mRNA in 18 patients. The sensitivity and negative predictive value (NPV) for HCMV‐disease was 100% for all tests. The PPV for symptomatic HCMV‐infection was 47% for pp67 mRNA. In contrast, the PPV of pp65‐antigenemia (using a threshold of > 2/200 000 cells) and quantitative PCR (using a cutoff of > 5000 copies/mL) were 80% and 89%, respectively. A cost analysis revealed symptom‐triggered or preemptive treatment was less expensive than general ganciclovir prophylaxis, if the incidence of CMV disease was low (<30%).

Short (1-10 cm) Superficial Femoral Artery Occlusions: Results of Treatment with Excimer Laser Angioplasty

Purpose: To evaluate the safety and long-term results after laser angioplasty of short occlusions of the superficial femoral artery (SFA). Methods: In a prospective trial in 312 patients with short occlusions of the SFA excimer laser angioplasty for recanalization was applied. The average occlusion length of the SFA was 7.5 cm (range 1–10 cm). The recanalization attempt was done using either a cross-over technique from the contralateral femoral artery (278 patients), antegrade technique (16 patients) or transpopliteal technique (18 patients). Results: Percutaneous transluminal laser angioplasty (PTLA) produced successful recanalization of the SFA in 286 of 312 patients (91.7%). In 26 patients (8.3%) recanalization was not possible. The reason for the unsuccessful PTLAs was obstructing calcified materialn = 8) which was resistant to laser application. In nine cases obstructing calcifications resulted in positioning of the laser catheter in subintimal tissue or perforation of the SFA. In another four patients there was an aberrant anatomy of the SFA which resulted in a direct vessel injury after advancing the laser catheter. In five patients subintimal recanalization failed. After a follow-up period of 36 months there was a primary, primary assisted and secondary patency rate of 49.2%, 76.5% and 86.3%. Conclusion:Excimer laser angioplasty of short occlusions of the SFA is a feasible procedure with a low failure rate. Long-term results are promising but additional interventions are required in most patients to achieve a patency rate of 86.3% after 3 years. Further studies are needed to compare the clinical outcome of PTLA and PTA in short occlusions of the SFA.